Isoprostane (8-Epiprostaglandin F_2α) Plasma Concentration and Aspirin Resistance in Patients after Ischaemic Stroke.

Background The limited efficacy of secondary prevention for ischaemic stroke may be partially related to aspirin resistance leading to continuous generation of intraplatelet thromboxane A₂. Besides other underlying metabolic mechanisms, an oxidant stress along with nonenzymatic biosynthesis of isoprostanes supporting the platelet activation has been suggested. Aims We analyzed the incidence of aspirin resistance in survivors of ischaemic stroke and compared the usefulness of some platelet tests designed for its laboratory exploration. Also we searched for relationship between isoprostane concentration and results of platelet function tests.

Material and Methods Forty four patients, at least a month after acute onset of ischaemic stroke were included into the study. All of them have been receiving 75–150 mg aspirin daily at least for a month. The control group for 11-dehydro Thromboxane B₂ measurements consisted of 12 healthy volunteers. The platelet function was investigated by platelet aggregation tests induced by either ADP (3.5 and 5.0 μM), collagen (2 μg/ml) or arachidonic acid (AA) (0.6 mM) and by measurement of closure time in PFA-100 analyzer. Thromboxane A₂ metabolite - 11-dehydro Thromboxane B₂ (11-dTxB₂) and isoprostane - 8-epi Prostaglandin F_2α (8-epiPgF_2α) plasma concentration by immunoenzymatic method (EIA Kits from Cayman Chemicals) were also determined. The aspirin ingestion was controlled by diminished intraplatelet concentration of malonyldialdehyde. Aspirin resistance has been determined by the following criteria: the intensity of platelet aggregation induced by ADP >60%, collagen >70%, AA >20%, PFA-100 closure time <165 s and 11-dTxB₂ concentration >mean of the control group minus SD.

Results Table 1 Statistically significant inverse correlations have been found between the plasma concentration of 11-dTxB₂ and PFA-100 (Col/Epi) closure time (r= −0.31; p= 0.039) as well as between plasma concentration of 8-epiPgF_2α and PFA-100 (Col/Epi) closure time (r= −0.36; p= 0.019).

Summary/conclusions

1. Laboratory platelet function tests reveal aspirin resistance in almost half of patients after ischaemic stroke.

2. The most significant correlation has been found between plasma concentration of 11-dehydro Thromboxane B₂ and PFA-100 closure time.

3. An important interrelationship observed between PFA-100 closure time and plasma concentration of 8-epi Prostaglandin F_2α may support the hypothesis of nonenzymatic production of isoprostanoids with platelet proaggregatory activity, playing a role in aspirin resistance.